DNCE方案治疗复发或难治的侵袭性非霍奇金淋巴瘤

目的 探讨DNCE方案作为二线解救方案治疗复发或难治的侵袭性非霍奇金淋巴瘤(NHL)的有效性和安全性.方法 经病理学或组织学证实的、且一线CHOP方案治疗后进展的侵袭性恶性NHL患者69例,按信封法随机分为DNCE方案组与DICE方案组.其中DICE组37例,采用地塞米松(DXM)20 mg,静脉滴注,d1～d4;异环磷酰胺(IFO)1 S/m2,静脉滴注,d1～d4;Mesna解救400 mg,静脉滴注q8h,d1～d4;顺铂(DDP)25 mg/m2,静脉滴注,d1～d4;依托泊苷(Vp-16)100 ms/m2,静脉滴注,d1～d4.21～28d为1个周期.DNCE组32例,采用DXM、DDP、Vp-16的剂量与DICE方案相同;NVB 25 ms/m2,静脉滴注,d1和d5.21～28d为1个周期.所有患者均完成≥2个周期的化疗.结果 DNCE组中,完全缓解(CR)6例,部分缓解(PR)12例,有效率为56.3%(18/32);DICE组中,CR 4例,PR 13例,有效率为45.9%(17/37).DNCE组的疗效优于DICE组,但两组间差异无统计学意义(P>0.05).DICE组的1、3、5年生存率分别为86.5%、58.3%和42.9%,DNCE组分别为87.5%、63.2%和38.5%,两组间差异无统计学意义(P>0.05).两组主要的不良反应为骨髓抑制和消化道反应,表现为粒细胞、血小板减少及恶心、呕吐等.DNCE组的骨髓毒性轻于DICE组,差异有统计学意义(P<0.05).结论 DNCE方案治疗侵袭性NHL的疗效肯定,骨髓毒性较DICE方案为轻,是侵袭性NHL患者安全有效的解救治疗方案.     

ESHAP方案治疗复发或难治性侵袭性非霍奇金淋巴瘤

 【摘要】　目的　观察ESHAP方案作为解救化疗方案治疗复发或难治性侵袭性非霍奇金淋巴瘤（NHL）的疗效和安全性。方法　选取38例复发或难治性侵袭性NHL患者，使用ESHAP方案（依托泊苷、甲泼尼龙、顺铂、阿糖胞苷）作为解救方案进行化疗。结果　38例患者各接受了2～6个周期ESHAP方案化疗，总的客观有效率为55.3 %，完全缓解率26.3 %；主要不良反应为骨髓抑制伴感染，均可耐受。结论　ESHAP方案是治疗复发或难治性侵袭性NHL安全有效的解救方案之一。     

Phase II study of paclitaxel and estramustine in patients with recurrent and refractory non-Hodgkin lymphoma

BACKGROUND: The current study was conducted to evaluate the efficacy of paclitaxel, administered weekly or once every 3 weeks, in combination with oral estramustine phosphate (EMP) in patients with recurrent or refractory aggressive non-Hodgkin lymphoma (NHL). METHODS: Between February 1996 and February 2001, 23 patients with recurrent NHL were enrolled onto this Phase II trial. The median age for all patients was 65 years (range, 27-80 years). The initial 12 patients (who received a mean number of 2.4 prior treatments, including 1 patient who received a prior peripheral blood stem cell transplant) received paclitaxel at a dose of 175 mg/m2 given as a 3-hour intravenous infusion every 21 days. The next 11 patients (who received a mean number of 2.8 prior treatments, including 1 patient who received prior peripheral blood stem cell transplant) were registered (1 patient refused treatment) to receive paclitaxel at a dose of 80 mg/m2 as a 1-hour intravenous infusion weekly for 6 weeks of an 8-week cycle. All patients received EMP at a dose of 600 mg/m2 orally per day beginning the day prior to each dose of paclitaxel for a total of 3 days. RESULTS: When paclitaxel was administered every 21 days, 4 partial responses were observed in 12 evaluable patients (33.3%). The median survival was 147 days. The median duration of response was 102 days (range, 42-127 days) and the median time to disease progression was 66 days. Grade 3 and Grade 4 neutropenia (according to the revised version of the Common Toxicity Criteria of the National Cancer Institute) were observed in 5 patients (42%) in this group. In an attempt to reduce the incidence of myelosuppression, paclitaxel dosing was changed to weekly dosing. In the cohort of patients receiving weekly paclitaxel, an objective response was reported to occur in 3 (1 complete response and 2 partial responses) of 11 evaluable patients (27%). The median survival was 132 days (range, 33-462 days). The median duration of response was 64 days and the median time to disease progression was 57 days. There was no significant difference noted between the cohort receiving paclitaxel three times weekly and those receiving paclitaxel weekly with regard to overall survival and time to disease progression (P = 0.7 and P = 0.8, respectively by the log-rank test). Grade 3 or 4 neutropenia was observed in only 2 of 11 patients (18%) in the weekly paclitaxel group. There were no significant differences noted in terms of thrombocytopenia, anemia, nausea, anorexia, or fatigue between the treatment groups. CONCLUSIONS: Paclitaxel given once weekly or three times weekly, in combination with oral EMP, was found to have comparable efficacy in patients with recurrent NHL, with an overall response rate of 30%. The response rate was found to be higher than that reported in prior studies of paclitaxel as a single agent in the treatment of NHL, suggesting that EMP may enhance paclitaxel efficacy in patients with NHL. Hematologic toxicity was diminished when paclitaxel was administered on a weekly schedule. The minimal myelotoxicity of weekly paclitaxel makes this a potentially attractive agent for combination regimens for patients with recurrent/refractory NHL.     

Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma

BACKGROUND: Oxaliplatin is a platinum derivative with a broad range of anticancer activity. The objective of the current Phase II trial was to investigate the activity of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma (NHL). METHODS: Patients with recurrent and refractory NHL who received a maximum of 3 previous chemotherapy regimens were considered eligible if they had an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Oxaliplatin was administered in an outpatient setting at a dose of 130 mg/m(2) by 2-hour intravenous infusion every 21 days for < or = 6 cycles in the absence of disease progression. RESULTS: Thirty-one patients (23 with aggressive NHL and 8 with indolent NHL) were enrolled, of whom 30 were assessable for toxicity, response, and survival. The median patient age was 62 years, and 20% of the patients previously received platinum-containing therapy. Eighty-three percent of the patients were refractory to their last treatment regimens. Grade 3 and 4 toxic effects (according to the National Cancer Institute's Common Toxicity Criteria [version 2.0]) included sensory neuropathy (10%), neutropenia (17%), and thrombocytopenia (20%). Objective responses occurred in 8 (27%; 95% confidence interval, 13-47%) of the patients. Responses were observed in platinum-naive patients as well as in those previously treated with platinum. The overall median failure-free survival duration was 3.0 months (range, 0.1-18.1 months). CONCLUSIONS: Oxaliplatin had favorable single-agent activity in previously treated patients with refractory lymphoma. The favorable safety profile and the ease of its administration in outpatient settings warrant investigating it in combination with other active drugs for the treatment of recurrent and refractory NHL.     

Repeated radioimmunotherapy with 131I-rituximab for patients with low-grade and aggressive relapsed or refractory B cell non-Hodgkin lymphoma

Purpose

A single treatment of ¹³¹I-rituximab in patients with B cell non-Hodgkin lymphoma (NHL) showed a modest rate of response (29 %) in a relatively short duration (median 2.9 months). On the basis of this result, we investigated whether repeated treatment with ¹³¹I-rituximab could improve the response.

Patients and methods

Thirty-one patients with relapsed or refractory B cell NHL received unlabeled rituximab (70 mg) immediately prior to the administration of a therapeutic dose of ¹³¹I-rituximab. The tumor response was evaluated 1 month later by contrast-enhanced ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography. Radioimmunotherapy (RIT) was repeated at 4-week intervals.

Results

A total of 87 cycles of RIT were administered. Repeated RIT yielded twofold increases in response rate (68 %) and in median response duration (8.6 months). This protocol also induced a favorable response in patients with an aggressive histology compared to that induced by a single treatment (50 vs. 9 %, respectively, p = 0.063). The toxicities were principally hematologic with grade 4 thrombocytopenia occurring in 12 % and neutropenia occurring in 17 % of the 85 assessable cycles.

Conclusions

Compared to a single treatment, repeated RIT with ¹³¹I-rituximab increased the response rate and duration for patients with relapsed or refractory B cell NHL, including those with an aggressive histology.     

Dexa-BEAM as salvage therapy in patients with primary refractory aggressive non-Hodgkin lymphoma

Although aggressive NHL in relapse after remission can still be cured by second-line treatment followed by high-dose therapy and autologous stem cell transplantation, the long-term prognosis of patients who fail to obtain remission after first-line therapy remains extremely poor. We retrospectively evaluated a series of 29 consecutive patients with primary refractory high-grade NHL who were treated with Dexa-BEAM (DB) as uniform salvage therapy at a single institution. Twenty-nine patients with aggressive NHL primary refractory to CHOP or CHOP-like induction therapy with a median age of 47 (range, 22 - 64) years received 1 - 2 cycles of DB and were candidates for subsequent autologous stem cell (PBSC) mobilization and transplantation (PBSCT). Follow-up of all patients was updated in March 2004. Eight of 29 patients (28%) responded to one cycle of DB (1 complete/7 partial remissions); 2 of whom are alive after PBSCT (1 autologous/1 matched unrelated donor), 1 patient died after autologous PBSCT. Reasons for failure to proceed to high-dose therapy in spite of response to DB were recurrent progressive disease (n = 2), septicemia (n = 1), and allogeneic transplant-related mortality after mobilization failure to DB (n = 2). Twenty-one patients failed to respond to DB and died of progressive disease. Overall survival was 7% after 41 months. We conclude that Dexa-BEAM salvage therapy is not effective in patients with truly primary refractory high-grade NHL. The efficiency of rituximab combined with Dexa-BEAM or novel chemotherapeutic strategies needs to be established.     

Usefulness of weekly administration of paclitaxel for advanced or recurrent gastric cancer

We report herein the efficacy and feasibility of weekly administration of paclitaxel for advanced/recurrent gastric cancer retrospectively. Eleven patients with advanced or recurrent gastric cancer who had received prior chemotherapy were treated with this regimen. Seventy mg of paclitaxel per m2 dissolved in 250 ml 5% glucose was administered by 1-hour intravenous infusion once a week for 3 weeks followed by 1 week rest. To avoid hypersensitivity reactions, the following short premedication was given to all the patients 1 hour before paclitaxel treatment: Dexamethasone 20 mg intravenously (i.v.), diphenhydramine 50 mg i.v., and ranitidine 50 mg i.v. Treatment cycle was 1 to 23 with an average cycle of 5.4. The response rate was 33% (2/6 with measurable lesions), the median time to progression was 104 days, and the median survival time was 160 days. Grade 3 neutropenia occurred in 27.2% of the patients. Weekly paclitaxel may be a promising regimen as a second-line chemotherapy for advanced/recurrent gastric cancer. However, special attention needs to be paid to the neutropenic adverse effect in gastric cancer patients with poor performance status than 2 (greater).     

含盖诺化疗方案治疗复发性或难治性非霍奇金淋巴瘤18例临床分析

目的探讨含国产盖诺的联合化疗方案治疗复发性或难治性非霍奇金淋巴瘤的疗效和毒副作用.方法采用NVB 30 mg/m2,ivgtt,d1,d5;DDP 30 mg/m2,ivgtt,d1～3;Ara-c 100 mg/m2,ivgtt,d1～2;PDN 60 mg/m2,口服,d1～5.3周为一个化疗周期.结果总有效率(CR PR)为72.2%,其中完全缓解(CR)2例,部分缓解(PR)11例.毒副反应主要是轻度的胃肠道反应,少数患者出现严重的骨髓抑制.结论含国产盖诺的联合化疗方案对复发性或难治性非霍奇金淋巴瘤有较好的疗效,是一种值得进一步验证的补救性化疗方案.     

A phase II study of weekly paclitaxel for advanced or recurrent breast cancer

The present study investigated the efficacy and safety of weekly administration of paclitaxel (PTX) for 37 patients with advanced or recurrent breast cancer. PTX was administered at a dose of 60 mg/m(2), 6 times every 8 weeks. The mean number of treatment cycles was 2.1, and the mean number of administrations was 12.7. Response rate was 35.1%. Two patients achieved CR, 11 PR, 13 NC (3 patients of long NC), 9 PD, and 2 NE. The clinical benefit rate (CR+PR+NC) was 70.3%. Median survival time was 733 days, and median time to treatment failure was 151 days. Grade 3 or more leucopenia and neutropenia occurred in 3 of patients (8.1%), and no patients showed hypersensitivity reaction after administration of PTX. Weekly PTX (60 mg/m(2)) is one of the treatment options in advanced or recurrent breast cancer from the standpoint of palliation.     

侵袭性T细胞非霍奇金淋巴瘤的化疗

T细胞非霍奇金淋巴瘤是一组具有独特临床和病理特征的疾病,与B细胞淋巴瘤相比,侵袭性更强,化疗敏感性差。为探索有效的治疗方案,近年来,新的药物如吉西他滨、靶向药物联合化疗及高剂量化疗联合造血干细胞移植被研究用于治疗T细胞淋巴瘤,并取得了一些进展。     

利妥昔单抗联合二线化疗药物治疗老年人复发或难治性淋巴瘤

目的 研究利妥昔单抗联合二线化疗药物对老年人复发和难治性非霍奇金淋巴瘤(NHL)的治疗效果及安全性.方法 采用利妥昔单抗联合二线化疗药物治疗复发和难治性NHL患者12例.结果 12例共治疗38个周期,总有效(CR+PR)8例,有效率66.7%,临床收益(CR+PR+SD)11例,收益率91.3%.1年无进展生存率和总生存率分别为41.0%和50.0%.不良反应以自细胞和血小板减少最为常见,但均可耐受.结论利妥昔单抗联合二线化疗方案治疗老年人复发和难治性NHL安全有效,且能耐受.     

Combined chemotherapy with weekly paclitaxel and carboplatin for recurrent and refractory epithelial ovarian cancer--phase I study

The current initial standard chemotherapy for advanced ovarian cancer is a regimen with a combination of platinum and taxane. However, the 5-year survival rate remains at 40% or lower, and the recurrence rate is as high as 70-80%. Second-line chemotherapy for recurrent cases has not yet been established. We conducted a phase I study of combined chemotherapy with paclitaxel (TXL) and carboplatin (CBDCA) administered weekly for recurrent and refractory ovarian cancer. The subjects were patients with a histopathologically confirmed diagnosis of malignant epithelial ovarian cancer, with recurrent or refractory disease after the initial chemotherapy. TXL was administered at escalating concentrations up to 60-100 mg/m(2), while the dose of CBDCA was fixed at an AUC of 2. In regard to the dosing schedule, premedication was performed as defined before TXL administration, and TXL and CBDCA were administered, in that order, by intravenous infusion for over at least 1 hour. The 4-week period, including the administration of both drugs on Day 1, 8, and 15, was regarded as one course of treatment. No cases developed grade 4 hematoxicity, but leukopenia and neutropenia occurred. All cases of leukopenia of step 4 and step 5 developed grade 3 leukopenia. Grade 2 thrombocytopenia was one example at a low rate. Non-hematological toxicity included neuropathy, arthralgia and muscle pain, but none of the patients developed grade 3 or 4. The response rate was 41.7% (5/12). The response rate of cases administered over TXL 80 mg was 66.7% (4/6). Based on these results,the following dose schedule was recommended for planning and designing a phase II study in the future: CBDCA AUC 2+TXL 80 mg/m(2) (Days 1, 8, and 15 q 4 weeks).     

Low-dose weekly paclitaxel therapy proved useful for a case of recurrent gastric cancer with clinically latent hepatic cirrhosis

The patient was a 68-year-old-man who suffered from recurrent peritoneal gastric cancer. He was initially treated with TS-1 as an outpatient. However, his serum CEA level elevated in March 2004, and he complained of epigastric pain in June. A chest and abdominal CT revealed lung and local recurrence. He began weekly paclitaxel as second-line chemotherapy in September. Paclitaxel was infused once a week for two weeks as one cycle, at a dose of 60 mg because of the clinically latent hepatic cirrhosis. One month after the first infusion therapy, epigastric pain was greatly reduced. A CT scan showed the lung metastasis had disappeared and the size of the tumor around the anastomosis was reduced to 50% after 2 months. The toxic events were appetite loss (grade 2) and alopecia (grade 2).     

Results of MIME salvage regimen for recurrent or refractory lymphoma

Based on encouraging results of two previous ifosfamide-VP-16 salvage combinations, methyl-gag was added to ifosfamide, methotrexate, and etoposide (VP-16). This combination is called MIME. A total of 208 patients with recurrent lymphoma were treated with this regimen. Response rates were 24% for complete remission and 36% for partial remission. The MIME regimen was more effective in patients who were treated after being off front-line therapy for longer than 6 months. However, responses were also seen in patients with disease clearly resistant to front-line therapy, suggesting that MIME was at least partially non-cross-resistant with front-line doxorubicin-containing regimens. The 15-month median relapse-free survival of complete responders and the 9-month overall median survival time for all patients treated were both similar to results from previous ifosfamide-VP-16 combination use. This regimen has been effective in the treatment of patients with recurrent or refractory lymphoma, but cannot be considered curative in the majority of cases.     

Irinotecan hydrochloride for the treatment of recurrent and refractory non-Hodgkin lymphoma: a single institution experience

BACKGROUND: Irinotecan hydrochloride (CPT-11) has a broad range of antitumor activity and has demonstrated little cross-resistance with doxorubicin or vincristine. In the current study, the authors investigated the efficacy and adverse effects of irinotecan in the treatment of recurrent and refractory non-Hodgkin lymphoma, for which current therapies appear to be unsatisfactory. METHODS: Irinotecan was administered by intravenous infusion at a dose of 40 mg/m(2)/day for 3 days, and this regimen was repeated 2-3 times at weekly intervals, followed by 2 weeks off therapy. The subjects were 48 patients with recurrent or refractory non-Hodgkin lymphoma. The histologic classification (Working Formulation) was low grade in 8 patients, intermediate grade in 36 patients, high grade in 1 patient, and other (angiocentric lymphoma, Ki-1 lymphoma, and unidentified) in 3 patients. RESULTS: Forty-five patients were determined to be evaluable. Therapy resulted in a complete disease remission in 2 patients and a partial remission in 15 patients. The response rate was 37.8%. The median duration of response was 64 days and the median time to disease progression was 77 days. The median survival time was 422 days. Major adverse reactions included myelosuppression and gastrointestinal toxicity. Leukopenia, anemia, and thrombocytopenia of Grade 3 or 4 (according to the National Cancer Institute Common Toxicity Criteria) was observed in 63.0%, 30.4%, and 6.5% of the patients, respectively, and Grade 3 or 4 diarrhea occurred in 30.4% of patients. Treatment was withdrawn because of diarrhea in three patients. Because of myelosuppression and diarrhea, approximately 67% of the patients required changes to the regimen, including dose reduction, prolongation of the interval between treatments, and reducing the number of days of consecutive treatment. CONCLUSIONS: The results of the current study suggest the activity of irinotecan as salvage therapy for patients with recurrent and refractory non-Hodgkin lymphoma. However, the optimum dosing schedule remains to be determined.     

Efficacy of weekly administration of paclitaxel for advanced or recurrent gastric cancer with peritoneal dissemination

We report 3 gastric cancer patients with peritoneal dissemination who failed to take TS-1 due to adverse effects and who were successfully treated with weekly paclitaxel administered intravenously. The patients were 2 men and 1 woman from 73 to 82 years in age. The histological types of gastric cancer were undifferentiated adenocarcinoma in all cases. Intravenous infusion of TXL (62-80 mg/m2) after short premedication was continued for 3 weeks followed by 1 week rest. Clinical symptoms, including ascites and intestinal obstruction, improved only after administration of 1 cycle in all patients. Except for 1 event with grade 3 neutropenia, no major adverse reactions were observed. Weekly administration of paclitaxel may be a promising chemotherapy for controlling peritoneal metastasis and improving the quality of life of patients with advanced or recurrent gastric cancer.     

盐酸吉西他滨治疗复发性或难治性非霍奇金淋巴瘤

目的：观察盐酸吉西他滨联合顺铂（DDP）、强的松（PDN）对复发性或难治性进展型非霍奇金淋巴瘤的疗效和毒副反应。方法：盐酸吉西他滨1000mg/m^2,d1,d8，静脉滴注；DDP 25mg/m^2，d1-3，静脉滴注；PDN 60mg/m^2,d1-5，口服。以3－4周为一个化疗周期。15例复发性或难治性进展型非霍奇金淋巴瘤患者，疗程不少于3个周期。结果：15例患者中，11例获得缓解，占73．3％。其中完全缓解（CR）5例，部分缓解（PR）6例。6例具有B类症状的患者中，4例症状消失，1例明显改善，1例无改善。化疗毒副作用主要为轻度的胃肠道反应，极少数患者出现严重的骨髓抑制。结论：盐酸吉西他滨联合DDP、PDN对复发性或难治性进展型非霍奇金淋巴瘤有较好的近期疗效，能明显改善患者症状，且大部分患者可以承受其毒性，是一个值得进一步验证的补救性化疗方案。     

MINE-ESHAP联合方案治疗难治或复发性非霍奇金淋巴瘤28例

目的 探讨MINE-ESHAP联合方案治疗难治性或复发性非霍奇金淋巴瘤(NHL)的疗效.方法 采用MINE-ESHAP联合方案治疗难治性或复发性NHL 28例.结果 28例患者中,CR 11例(39.3%),PR 6例(21.4%),SD 5例(17.9%),进展或恶化5例(17.9%),中位生存时间28.5个月.1例死于骨髓抑制期感染(3.6%).不良反应主要为消化道症状和骨髓抑制.结论 MINE-ESHAP方案对部分难治性或复发性NHL患者有效,不良反应可以耐受,可用于对其他化疗方案无效的难治性或复发性NHL.